Analysis of infections among patients with historical culture positive for extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae: Is ESBL-targeted therapy always needed?

Objective: Among patients with a history of ESBL infection, uncertainty remains regarding whether all of these patients require ESBL-targeted therapy when presenting with a subsequent infection. We sought to determine the risks associated with a subsequent ESBL infection to help inform empiric antibiotic decisions. Methods: A retrospective cohort study of adult patients with positive index culture for Escherichia coli or Klebsiella pneumoniae (EC/KP) receiving medical care during 2017 was conducted. Risk assessments were performed to identify factors associated with subsequent infection caused by ESBL-producing EC/KP. Results: In total, 200 patients were included in the cohort, 100 with ESBL-producing EC/KP and 100 with ESBL-negative EC/KP. Of 100 patients (50%) who developed a subsequent infection, 22 infections were ESBL-producing EC/KP, 43 were other bacteria, and 35 had no or negative cultures. Subsequent infection caused by ESBL-producing EC/KP only occurred when the index culture was also ESBL-producing (22 vs 0). Among those with ESBL-producing index culture, the incidences of subsequent infection caused by ESBL-producing EC/KP versus other bacterial subsequent infection were similar (22 vs 18; P = .428). Factors associated with subsequent infection caused by ESBL-producing EC/KP include history of ESBL-producing index culture, time ≤180 days between index culture and subsequent infection, male sex, and Charlson comorbidity index score >3. Conclusions: History of ESBL-producing EC/KP culture is associated with subsequent infection caused by ESBL-producing EC/KP, particularly within 180 days after the historical culture. Among patients presenting with infection and a history of ESBL-producing EC/KP, other factors should be considered in making empiric antibiotic decisions, and ESBL-targeted therapy may not always be warranted.

Clinical impact of a multiplex rapid diagnostic pneumonia panel in critically ill patients.

Objective: To evaluate the clinical impact of the BioFire FilmArray Pneumonia Panel (PNA panel) in critically ill patients. Design: Single-center, preintervention and postintervention retrospective cohort study. Setting: Tertiary-care academic medical center. Patients: Adult ICU patients. Methods: Patients with quantitative bacterial cultures obtained by bronchoalveolar lavage or tracheal aspirate either before (January-March 2021, preintervention period) or after (January-March 2022, postintervention period) implementation of the PNA panel were randomly screened until 25 patients per study month (75 in each cohort) who met the study criteria were included. Antibiotic use from the day of culture collection through day 5 was compared. Results: The primary outcome of median time to first antibiotic change based on microbiologic data was 50 hours before the intervention versus 21 hours after the intervention (P = .0006). Also, 56 postintervention regimens (75%) were eligible for change based on PNA panel results; actual change occurred in 30 regimens (54%). Median antibiotic days of therapy (DOTs) were 8 before the intervention versus 6 after the intervention (P = .07). For the patients with antibiotic changes made based on PNA panel results, the median time to first antibiotic change was 10 hours. For patients who were initially on inadequate therapy, time to adequate therapy was 67 hours before the intervention versus 37 hours after the intervention (P = .27). Conclusions: The PNA panel was associated with decreased time to first antibiotic change and fewer antibiotic DOTs. Its impact may have been larger if a higher percentage of potential antibiotic changes had been implemented. The PNA panel is a promising tool to enhance antibiotic stewardship.

A comparison of active versus passive methods of responding to rapid diagnostic blood culture results.

Objective: To compare 2 methods of communicating polymerase chain reaction (PCR) blood-culture results: active approach utilizing on-call personnel versus passive approach utilizing notifications in the electronic health record (EHR). Design: Retrospective observational study. Setting: A tertiary-care academic medical center. Patients: Adult patients hospitalized with ≥1 positive blood culture containing a gram-positive organism identified by PCR between October 2014 and January 2018. Methods: The standard protocol for reporting PCR results at baseline included a laboratory technician calling the patient's nurse, who would report the critical result to the medical provider. The active intervention group consisted of an on-call pager system utilizing trained pharmacy residents, whereas the passive intervention group combined standard protocol with real-time in-basket notifications to pharmacists in the EHR. Results: Of 209 patients, 105, 61, and 43 patients were in the control, active, and passive groups, respectively. Median time to optimal therapy was shorter in the active group compared to the passive group and control (23.4 hours vs 42.2 hours vs 45.9 hours, respectively; P = .028). De-escalation occurred 12 hours sooner in the active group. In the contaminant group, empiric antibiotics were discontinued faster in the active group (0 hours) than in the control group and the passive group (17.7 vs 7.2 hours; P = .007). Time to active therapy and days of therapy were similar. Conclusions: A passive, electronic method of reporting PCR results to pharmacists was not as effective in optimizing stewardship metrics as an active, real-time method utilizing pharmacy residents. Further studies are needed to determine the optimal method of communicating time-sensitive information.

Antiviral Pharmacology: A Standardized Patient Case for Preclinical Medical Students.

Introduction: Pharmacology is an important learning topic in preclinical medical education. Simulated patient encounters allow students to apply basic science knowledge in a clinical setting and have been useful in previous studies of pharmacology education. We developed a standardized patient (SP) encounter to reinforce antiviral pharmacology content for first-year medical students. Methods: Students were instructed to recommend a medication for shingles during an SP encounter and to answer questions from the SP on mechanism of action and adverse effects. Students then attended a large-group debrief session. Following the activity, students evaluated the exercise through a voluntary survey. For knowledge assessment, students were randomized into two groups to complete three multiple-choice questions either before or after the learning activity. Results: In 2020 and 2021, 144 and 145 students, respectively, participated. In 2020, there was no significant difference in the proportion of correct answers between the pre- and postsimulation groups (p > .05). In 2021, the postsimulation group significantly outperformed the presimulation group in knowledge of mechanism of action (p < .01) and adverse effects (p < .01), but no difference was seen between the groups regarding medication selection (p = .27). Most learners assessed the instructional design as effective for the tasks assigned. Discussion: This SP activity provided an opportunity for early medical students to practice integrating antiviral pharmacology knowledge into a patient encounter and was well received by learners. The instructional method offers a clinically relevant approach for reinforcing pharmacology knowledge for preclinical medical students.

Impact of an Interprofessional Collaborative Quality Improvement Initiative to Decrease Inappropriate Thyroid Function Testing.

Background: Published data show that thyroid function laboratory tests are often ordered inappropriately in the acute care setting, which leads to unnecessary costs and inappropriate therapy decisions. Pilot data at our institution indicated that approximately two-thirds of the thyroid-stimulating hormone (TSH) laboratories were unnecessary, correlating to a potential cost avoidance of more than $20,000 annually. The purpose of this study was to improve the appropriateness of thyroid function test ordering with a multipronged initiative. Methodology: This controlled, single-center, before and after study included inpatients or emergency department (ED) patients at Wake Forest Baptist Medical Center who were at least 18 years of age and had a TSH level ordered during the study period. Patients with a history of thyroid cancer were excluded. The initiative included an electronic ordering intervention, direct education of providers (medical residents, attendings, and clinical pharmacists), and distribution of pocket information cards with appropriate ordering criteria. The primary outcome was the number and percentage of inappropriate TSH tests ordered before and after implementing the 3 interventions. Secondary outcomes included cost savings, inappropriate changes in thyroid therapy based on improperly ordered tests, and the number of free T4 lab tests ordered on patients with a TSH within the therapeutic range. Results: All 3 interventions were implemented, except for education of ED residents and faculty, who chose to forgo the direct education component. Inappropriate ordering of TSH levels decreased from 63 to 50 (13% reduction, P = .062) after implementation. Inappropriate TSH ordering decreased across all services, except in the ED. Inappropriate Free T4 orders decreased from 191 to 133 (30% reduction, P = .01). There were no therapy changes based on inappropriate TSH orders. Extrapolated annual cost savings were approximately $6,000. Conclusion: This multipronged interprofessional collaborative quality improvement initiative was associated with a nonstatistically significant reduction in inappropriate TSH orders, statistically significant reduction in inappropriate free T4 orders, and cost savings. There was a reduction in inappropriate ordering across all services except the ED, which may have been due the ED not participating in the direct education component of the initiative.

Multicenter point prevalence evaluation of the utilization and safety of drug therapies for COVID-19 at the onset of the pandemic timeline in the United States.

KEY POINTS: In a multicenter point-prevalence study, we found that the rate of supportive care was high; among those receiving COVID-19 drug therapies, adverse reactions occurred in 12% of patients. PURPOSE: There are currently no FDA-approved medications for the treatment of coronavirus disease 2019 (COVID-19). At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. METHODS: We conducted a noninterventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19-targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). RESULTS: A total of 352 patients treated for COVID-19 at 15 US hospitals From April 18 to May 8, 2020, were included in the study. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies used included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 antagonists (9%). Five patients (7.5%) were receiving combination therapy. The rate of use of COVID-19-directed drug therapy was higher in patients with vs patients without a history of asthma (14.9% vs 7%, P = 0.037) and in patients enrolled in clinical trials (26.9% vs 3.2%, P < 0.001). Among those receiving drug therapy, 8 patients (12%) experienced an ADR, and ADRs were recognized at a higher rate in patients enrolled in clinical trials (62.5% vs 22%; odds ratio, 5.9; P = 0.028). CONCLUSION: While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy, including those enrolled in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 treatments.

Multicenter point-prevalence evaluation of the utilization and safety of drug therapies for COVID-19.

BACKGROUND: There are currently no FDA-approved medications for the treatment of COVID-19. At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. METHODS: We conducted a non-interventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19 targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). RESULTS: A total of 352 patients from 15 US hospitals were included. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 inhibitors (9%). Five patients (7.5%) were receiving combination therapy. Patients with a history of asthma (14.9% vs. 7%, p=0.037) and those enrolled in clinical trials (26.9% vs. 3.2%, p<0.001) were more likely to receive therapy. Among those receiving COVID-19 therapy, eight patients (12%) experienced an ADR, and ADRs were more commonly recognized in patients enrolled in clinical trials (62.5% vs 22%, OR=5.9, p=0.028). CONCLUSIONS: While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy including in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 therapies.

Impact of order entry alerts and modifications on doses of intravenous opioids dispensed during a national drug shortage.

PURPOSE: To address the intravenous (i.v.) opioid shortage, computer-based alerts and modifications were implemented over 2 phases beginning in August 2017 and February 2018, respectively. A study was conducted to assess the impact of these interventions on dispenses of intermittent doses of i.v. opioids during a national shortage. METHODS: A retrospective, single-center, pre- and postimplementation study was conducted to compare opioid dispenses from September 2017 through December 2017 (phase 1) and March 2018 through May 2018 (phase 2) with dispenses during the same time periods of the previous year (historical control periods). Dispense data for intermittent doses of i.v. fentanyl, hydromorphone, and morphine and select oral opioids were collected from automated dispensing cabinets (ADCs) located in nonprocedural areas. The primary endpoint was the percentage of total intermittent doses of i.v. and oral opioids that were dispensed for i.v. administration. A subanalysis accounting for unit type was conducted. Key secondary endpoints were the numbers of oral and i.v. opioid dispenses by month. RESULTS: The final analysis included data from 92 ADCs. The percentage of i.v. opioid dispenses significantly decreased, by 9.8% during phase 1 (P < 0.0001) and by 16.8% during phase 2 (P < 0.0001) compared to dispenses during the historical control periods. These decreases were significant across all unit types except pediatric units during phase 1. Average monthly dispenses of i.v. opioids were 49.9% and 74.2% fewer than dispenses during the historical control periods after the phase 1 and phase 2 implementations, respectively. CONCLUSION: Order entry alerts and modifications significantly decreased dispenses of intermittent doses of i.v. opioids during a national shortage, with demonstrated sustainability of decreases over 7 months.

Pharmacist involvement in a multidisciplinary initiative to reduce sepsis-related mortality.

PURPOSE: Pharmacy department contributions to a medical center's broad initiative to improve sepsis care outcomes are described. SUMMARY: Timely and appropriate antimicrobial therapy is a key factor in optimizing treatment outcomes in patients with severe sepsis or septic shock. The inpatient pharmacy at Wake Forest Baptist Health implemented standardized processes to reduce order turnaround time and facilitate prompt antibiotic administration as part of the hospital's multidisciplinary "Code Sepsis" initiative. The program includes (1) nurse-conducted screening for sepsis using a standard assessment instrument, (2) pager alerts notifying rapid-response, pharmacy, and other personnel of cases of suspected sepsis, (3) activation of an electronic order set including guideline-based antibiotic therapy recommendations based on local pathogen patterns, and (4) a protocol allowing pharmacists to select an antibiotic regimen if providers are busy with other patient care duties. Assessments conducted during and after implementation of the Code Sepsis initiative showed improvements in key program metrics. The mean ± S.D. time from receipt of a Code Sepsis page to antibiotic delivery was reduced to 14.1 ± 13.7 minutes, the mean time from identification of suspected sepsis to antibiotic administration was reduced to 31 minutes in the hospital's intensive care units and to 51 minutes in non-critical care units, and the institution's performance on a widely used measure of sepsis-related mortality improved dramatically. CONCLUSION: Implementation of the Code Sepsis initiative was associated with reductions in order turnaround time, time to antibiotic administration, and sepsis-related mortality.

The Addition of Intravenous Metronidazole to Oral Vancomycin is Associated With Improved Mortality in Critically Ill Patients With Clostridium difficile Infection.

BACKGROUND: The optimal therapy for critically ill patients with Clostridium difficile infection (CDI) is not known. We aimed to evaluate mortality among critically ill patients with CDI who received oral vancomycin (monotherapy) vs oral vancomycin with intravenous (IV) metronidazole (combination therapy). METHODS: A single-center, retrospective, observational, comparative study was performed. Patients with a positive C. difficile assay who received oral vancomycin while bedded in an intensive care unit (ICU) between June 2007 and September 2012 were evaluated. Patients meeting ≥3 of the following criteria were included: albumin <2.5 g/dL, heart rate >90 bpm, mean arterial pressure <60 mmHg, white blood cell count ≥15 000 cells/mL, age >60 years, serum creatinine ≥1.5 times baseline, or temperature ≥100.4°F. Patients in the combination therapy group received IV metronidazole within 48 hours after initiating vancomycin. Patients <18 years or with unrelated gastrointestinal disease were excluded. The primary outcome was in-hospital mortality. Patients were matched using Acute Physiology and Chronic Health Evaluation II scores. RESULTS: Eighty-eight patients were included, 44 in each group. Patient characteristics were similar although more patients in the combination group had renal disease. Mortality was 36.4% and 15.9% in the monotherapy and combination therapy groups, respectively (P = .03). Secondary outcomes of clinical success, length of stay, and length of ICU stay did not differ between groups. CONCLUSIONS: Our data are supportive of the use of combination therapy with oral vancomycin and IV metronidazole in critically ill patients with CDI. However, prospective, randomized studies are required to define optimal treatment regimens in this limited population of CDI patients.

Optimizing empiric antibiotic therapy in patients with severe ß-lactam allergy.

Antibiotic selection is challenging in patients with severe ß-lactam allergy due to declining reliability of alternate antibiotics. Organisms isolated from these patients may exhibit unique resistance phenotypes. The objective of this study was to determine which alternate antibiotics or combinations provide adequate empirical therapy for patients with ß-lactam allergy who develop Gram-negative infections at our institution. We further sought to determine the effects of risk factors for drug resistance on empirical adequacy. A retrospective analysis was conducted for adult patients hospitalized from September 2009 to May 2010 who had a severe ß-lactam allergy and a urine, blood, or respiratory culture positive for a Gram-negative organism and who met predefined criteria for infection. Patient characteristics, culture and susceptibility data, and predefined risk factors for antibiotic resistance were collected. Adequacies of ß-lactam and alternate antibiotics were compared for all infections and selected subsets. The primary outcome was adequacy of each alternate antibiotic or combination for all infections. One hundred sixteen infections (40 pneumonias, 67 urinary tract infections, and 9 bacteremias) were identified. Single alternate agents were adequate less frequently than ß-lactams and combination regimens. Only in cases without risk factors for resistance did single-agent regimens demonstrate acceptable adequacy rates; each factor conferred a doubling of risk for resistance. Resistance risk factors should be considered in selecting empirical antibiotics for Gram-negative pathogens in patients unable to take ß-lactams due to severe allergy.

Implementation of a Standardized Discharge Time-out Process to Reduce Prescribing Errors at Discharge.

BACKGROUND: To reduce prescribing errors occurring on discharge from the hospital, a standardized discharge time-out process was implemented on a general medicine service at Wake Forest Baptist Medical Center. In the time-out process, the multidisciplinary care team reviewed the patient's medical records together to determine the optimal discharge medication regimen. This regimen was recorded on a time-out form and then was used to develop the patient's discharge documents. OBJECTIVE: To evaluate the impact of a standardized discharge time-out process on prescribing errors that occur as patients are discharged from a general medicine service. METHODS: The medical records of all patients discharged from a general medicine service during 60-day periods before ("pre-group") and after ("post-group") implementation of a standardized discharge time-out process were retrospectively reviewed by an internal medicine physician to determine the presence of discharge prescribing errors. RESULTS: There were 142 and 124 evaluable patients in the pre- and post-groups, respectively. Compliance with the time-out process was 93% in the post-group. At least 1 prescribing error was detected in 49 (34.5%) of the discharges in the pre-group and 17 (13%) of the discharges in the post-group (P < .0001). All of the errors noted in the post-group occurred in discharges in which a clinical pharmacist was not involved. CONCLUSIONS: A multidisciplinary, standardized discharge time-out process was associated with a dramatic reduction in prescribing errors when patients were discharged from a general medicine service. The time-out process is one strategy to improve patient safety at hospital discharge.

Show me the money: long-term financial impact of an antimicrobial stewardship program.

The financial impact of an antimicrobial stewardship program in operation for more than 11 years was determined by calculating the reduction in antimicrobial expenditures minus program labor costs. Depending on the method of inflation adjustment used, the program was associated with average cost savings of $920,070 to $2,064,441 per year.

Short-term outcomes of an employer-sponsored diabetes management program at an ambulatory care pharmacy clinic.

PURPOSE: The impact of a collaborative, employer-sponsored diabetes management program on glycemic control and other clinical endpoints over 6-12 months is reported. METHODS: In a retrospective, chart-based evaluation, glycosylated hemoglobin (HbA(1c)) and related health status indicators were assessed among first-year enrollees in the Healthy Outcome Partnership for Employees (HOPE) with Diabetes Program, an ongoing program sponsored by the Wake Forest Baptist Health (WFBH) system. Diabetes management services were provided by pharmacists in collaboration with providers inside and outside the WFBH system. The primary endpoint was the mean change in HbA(1c) during follow-up averaging 8.2 months; secondary endpoints included changes in blood pressure, cholesterol, and triglyceride levels. RESULTS: Among the 98 patients included in the data analysis (75.5% women, 72.4% Caucasian), the mean HbA(1c) value decreased significantly during the study period (from 7.8% to 7.1%, p < 0.01); the proportion of patients at the recommended goal of an HbA(1c) of ≤7.0% rose from 40.8% to 56.1% (p < 0.01). HOPE Program enrollees also experienced significant improvements in mean triglyceride, total cholesterol, and blood pressure values (p < 0.05 for all). A subgroup of patients with initially poor glycemic control (HbA(1c) of ≥8.0%) had a mean HbA(1c) reduction of 1.7 percentage points during the study (p < 0.01), suggesting that the greatest benefits occurred in the highest-risk patients. CONCLUSION: Among patients seen for at least six months at an employer-sponsored ambulatory care diabetes clinic managed by pharmacists, significant improvements from baseline in clinical end-points including HbA(1c) and blood pressure were demonstrated.

Using local microbiologic data to develop institution-specific guidelines for the treatment of hospital-acquired pneumonia.

BACKGROUND: While current guidelines recommend consideration of local microbiologic data when selecting empiric treatment for hospital-acquired pneumonia (HAP), few specifics of how to do this have been offered. METHODS: We conducted a retrospective analysis of HAP pathogens in 111 consecutive patients who acquired HAP during July to December 2004 and had a corresponding positive culture finding for a bacterial pathogen. These data were used to develop institution-specific guidelines. RESULTS: The most common bacteria identified were Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa, which were associated with 38%, 25%, and 19% of pneumonias, respectively. Susceptibility of Gram-negative bacteria to piperacillin-tazobactam and cefepime was 80% and 81%, respectively. The isolation of organisms resistant to piperacillin-tazobactam or cefepime was significantly more frequent in patients who had been hospitalized > or = 10 days. Of Gram-negative isolates resistant to piperacillin-tazobactam or cefepime, ciprofloxacin was active against < 10%, while amikacin was active against > 80%. New treatment guidelines were developed that divided the American Thoracic Society/Infectious Diseases Society of America "late onset/risk of multidrug-resistant pathogens" group of patients into two subcategories: "early-late" pneumonias (< 10 days of hospitalization) and "late-late" pneumonias (> or = 10 days of hospitalization). Guideline-directed treatment regimens would be predicted to provide adequate initial therapy for > 90% of late-onset pneumonias at our institution. CONCLUSIONS: Current guidelines suggest adding either an aminoglycoside or a fluoroquinolone to beta-lactam therapy for empiric Gram-negative coverage. However, in our institution, adding ciprofloxacin would not appreciably enhance the likelihood of providing initial appropriate antibiotic coverage. This underscores the importance of employing a systematic analysis of local data when developing treatment guidelines.